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FLASH GENE
Symbol PON1 contributors: npt/mct - updated : 29-11-2017
HGNC name paraoxonase 1
HGNC id 9204
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer heteromer , oligo
HOMOLOGY
interspecies homolog to rattus Pon1 (80.56 pc)
homolog to murine Pon1 (81.97 pc)
Homologene
FAMILY
  • paraoxonase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
    text secreted by the liver and transported in the blood complexed to HDL
    basic FUNCTION
  • hydrolyzing the toxic metabolites of a variety of organophosphorous insecticides
  • may mediate an enzymatic protection of low density lipoproteins against oxidative modification
  • leading to anti-atherogenic effects by specifically binding to macrophage binding sites
  • having antioxidative and atheroprotective role
  • high-density lipoprotein (HDL)-bound enzyme that exerts antiatherogenic properties by protecting low-density lipoprotein (LDL)-cholesterol from oxidative modification
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS detoxification
    PATHWAY
    metabolism
    signaling
    a component
  • MPO, PON1, and high-density lipoprotein bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
    cell & other
  • binding to macrophage
    • REGULATION
    repressed by bile acids through the actions of NR1H4 and FGF19
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in atherosclerosis
    constitutional     --low  
    in patients with calcific aortic valve stenosis (AS) and its activity was inversely correlated with the severity of AS
    Susceptibility
  • to coronary heart disease but not myocardial infarction
  • atherosclerosis
  • pesticide poisoning
  • exsudative age-related macular degeneration
  • to abdominal aortic aneurysm (Giusti 2008)
  • Alzheimer disease (AD)
  • to sporadic amyotrophic lateral sclerosis
  • to attaining longevity
  • to strocke
    • Variant & Polymorphism SNP , other
  • Arg192 allele increased survival at extreme advanced age
  • polymorphism 192Q/R, 55M/L,and promoter variant 107C/T increases protection against coronary artery disease
  • -161[C/T] SNP in creasing the risk of Alzheimer
  • Q192R polymorphism increasing the risk of sporadic amyotrophic lateral sclerosis and associated with stroke and myocardial infarction
  • variants at codon 192 impact on the probability of attaining longevity
  • Q192R polymorphism could be an important risk factor for stroke
  • rs854563 associated with coronary atherosclerosis
  • multiple variants in PON influence serum paraoxonase activity, and low serum paraoxonase activity is a risk factor for AD
    • Candidate gene
    Marker
    Therapy target
  • for future cardio protection therapy via the macrophage PON1 binding sites
    • ANIMAL & CELL MODELS